The brain beta-endorphin system will be studied using anatomical, biochemical, and pharmacological techniques. This beta-endorphin system is anatomically distinct from the enkephalin system. The beta-endorphin positive neurons also exhibit ACTH-like immunoreactivity suggesting the presence of the 31 K precursor. Brain beta-endorphin will be studied as a potential neurotransmitter or neuromodulator. This will involve examining in more detail the anatomy and physiology of brain beta-endorphin in contrast to the pituitary system or to brain enkephalin. The techniques to be employed include receptor assays, radioimmunoassays, immunocytochemistry, and behavioral manipulations. Hypotheses concerning the role and interactions of opioids and other peptides are derived from examining the existing literature on morphine and ACTH, and on endocrine regulation of 31 K fragments. The role of beta-endorphin and ACTH in various behavioral states, including pain modulation and opiate addiction, tolerance, and dependence will be investigated.